@article{86b1da775f1942328d17d145b9c6c23f,
title = "A basophil-neuronal axis promotes itch",
abstract = "Itch is an evolutionarily conserved sensation that facilitates expulsion of pathogens and noxious stimuli from the skin. However, in organ failure, cancer, and chronic inflammatory disorders such as atopic dermatitis (AD), itch becomes chronic, intractable, and debilitating. In addition to chronic itch, patients often experience intense acute itch exacerbations. Recent discoveries have unearthed the neuroimmune circuitry of itch, leading to the development of anti-itch treatments. However, mechanisms underlying acute itch exacerbations remain overlooked. Herein, we identify that a large proportion of patients with AD harbor allergen-specific immunoglobulin E (IgE) and exhibit a propensity for acute itch flares. In mice, while allergen-provoked acute itch is mediated by the mast cell-histamine axis in steady state, AD-associated inflammation renders this pathway dispensable. Instead, a previously unrecognized basophil-leukotriene (LT) axis emerges as critical for acute itch flares. By probing fundamental itch mechanisms, our study highlights a basophil-neuronal circuit that may underlie a variety of neuroimmune processes.",
keywords = "IgE, allergy, atopic dermatitis, basophils, itch, leukotriene, mast cells, pruritus, sensory neurons",
author = "Fang Wang and Trier, {Anna M.} and Fengxian Li and Seonyoung Kim and Zhen Chen and Chai, {Jiani N.} and Mack, {Madison R.} and Morrison, {Stephanie A.} and Hamilton, {Jennifer D.} and Jinok Baek and Yang, {Ting Lin B.} and {Ver Heul}, {Aaron M.} and Xu, {Amy Z.} and Zili Xie and Xintong Dong and Masato Kubo and Hongzhen Hu and Hsieh, {Chyi Song} and Xinzhong Dong and Qin Liu and Margolis, {David J.} and Marius Ardeleanu and Miller, {Mark J.} and Kim, {Brian S.}",
note = "Funding Information: We thank Diane Bender and the Immunomonitoring Lab (IML) at the Andrew M. and Jane M. Burksy Center for Human Immunology & Immunotherapy Programs (ChiiPs). We also thank the In Vivo Imaging Core (IVIC) at the Washington University School of Medicine for their support of the intravital two-photon imaging studies. The Kim Lab is supported by NIAMS grants (K08-AR065577 and R01-AR070116), the American Skin Association, Doris Duke Charitable Foundation (to B.S.K.), and LEO Pharma. D.J.M. is supported by NIAMS grants (R01-AR060962 and R01-AR070873). M.J.M. is supported by NIAID grant (R01-AI077600). A.M.T. and M.R.M. were supported by NIAID training grant T32-AI716339. A.M.T. was also supported by the NIAID NRSA grant F30 AI154912. T.-L.B.Y. was supported by the Dermatology Foundation Dermatologist Investigator Research Fellowship (DIRF). The IML is a shared resource of the Alvin J. Siteman Cancer Center and is supported by the Andrew M. and Jane M. Bursky ChiiPs and NCI Cancer Center support grant (P30CA91842). F.W. and B.S.K. designed the experiments. F.W. performed the experiments and analyzed the data. F.L. contributed to calcium imaging and siRNA delivery. Z.X. and X.D. assisted with calcium imaging. S.K. and M.J.M. performed two-photon imaging and did imaging data analyses. Z.C. J.D.H. and M.A. provided human data of itch scores and assisted the analyses. D.J.M. provided human blood samples and clinical assessments of control subjects and patients with AD. M.R.M. J.N.C. and C.S.H. assisted with flow cytometry. M.R.M. contributed to the graphical abstract. A.M.T. J.B. A.Z.X. and S.A.M. assisted with behavioral assays. X.D. H.H. Q.L. and M.K. donated mice. F.W. A.M.T. T.-L.B.Y. A.M.V.H. and B.S.K. wrote the manuscript. B.S.K. supervised the project. B.S.K. has served as a consultant for AbbVie, ABRAX Japan, Almirall, AstraZeneca, Cara Therapeutics, Daewoong Pharmaceutical, Incyte, LEO Pharma, Lilly, Maruho, Menlo Therapeutics, OM Pharma, Pfizer, and Third Rock Ventures. He has also participated on the advisory board for Almirall, Boehringer Ingelheim, Cara Therapeutics, Kiniksa Pharmaceuticals, Menlo Therapeutics, Regeneron Pharmaceuticals, Sanofi Genzyme, and Trevi Therapeutics. He is stockholder of Locus Biosciences. All other authors declare that they have no relevant conflicts of interest. Funding Information: We thank Diane Bender and the Immunomonitoring Lab (IML) at the Andrew M. and Jane M. Burksy Center for Human Immunology & Immunotherapy Programs (ChiiPs). We also thank the In Vivo Imaging Core (IVIC) at the Washington University School of Medicine for their support of the intravital two-photon imaging studies. The Kim Lab is supported by NIAMS grants ( K08-AR065577 and R01-AR070116 ), the American Skin Association , Doris Duke Charitable Foundation (to B.S.K.), and LEO Pharma . D.J.M. is supported by NIAMS grants ( R01-AR060962 and R01-AR070873 ). M.J.M. is supported by NIAID grant ( R01-AI077600 ). A.M.T. and M.R.M. were supported by NIAID training grant T32-AI716339 . A.M.T. was also supported by the NIAID NRSA grant F30 AI154912 . T.-L.B.Y. was supported by the Dermatology Foundation Dermatologist Investigator Research Fellowship (DIRF). The IML is a shared resource of the Alvin J. Siteman Cancer Center and is supported by the Andrew M. and Jane M. Bursky ChiiPs and NCI Cancer Center support grant ( P30CA91842 ). Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2021",
month = jan,
day = "21",
doi = "10.1016/j.cell.2020.12.033",
language = "English",
volume = "184",
pages = "422--440.e17",
journal = "Cell",
issn = "0092-8674",
number = "2",
}